- Synthesis, biological evaluation and molecular modeling of imidazo[1,2-a]pyridine derivatives as potent antitubulin agents
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Two series of novel 5,7-diarylimidazo[1,2-a]pyridine-8-carbonitrile derivatives (3a–3q and 7a–7n) were designed by modification of CA-4 pharmacophore to develop colchicine targeted antitubulin agents. All compounds were efficiently synthesized and evaluated for their cytotoxicity against five selected cancer cell lines (HT-29, H460, A549, MKN-45 and SMMC-7721) which got an insight in structure and activity relationships (SARs). Several molecules (7e, 7f, 7h–7j and 7m) were disclosed to exhibit promising antiproliferative activity with IC50 values in double-digit nanomolar degree. Optimization toward these compounds led to the discovery of a promising lead 7e, which showed noteworthy potency with IC50 value ranging from 0.01 to 3.2?μM superior to CA-4 and Crolibulin. Importantly, immunofluorescence staining and colchcine competitive binding assay revealed that microtubule dynamics was disrupted by 7e by binding at the colchicine site of tubulin. Moreover, molecular docking studies suggested the binding of this mimic at colchcine-binding site is similar to Crolibulin, as was in conformity with the observed SARs for these compounds.
- Liu, Jin,Zuo, Daiying,Jing, Tongfei,Guo, Ming,Xing, Lingyun,Zhang, Wenyu,Zhao, Jianwen,Shen, Jiwei,Gong, Ping,Zhang, Dajun,Zhai, Xin
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Read Online
- Natural product Pimprinine derivative as well as preparation method and application thereof
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The invention discloses a Pimprinine derivative as shown in a formula III in the description. The invention also discloses a preparation method of the Pimprinine derivative, and a series of Pimprinine derivatives are synthesized by taking Pimprinine as a lead, combining the structural characteristics of Pimprinine, taking cheap and easily available indole as a raw material, modifying and transforming different sites of a framework structure of the indole and introducing different substituent groups. The Pimprinine derivative disclosed by the invention has good bactericidal activity, shows efficient and/or broad-spectrum bactericidal activity, and can be applied to crop diseases caused by fungi, bacteria and viruses.
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Paragraph 0047
(2021/07/31)
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- A radical addition and cyclization relay promoted by Mn(OAc)3?2H2O: Synthesis of 1,2-oxaphospholoindoles and mechanistic study
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Novel and efficient Mn(OAc)3?2H2O promoted radical addition-[4 + 1] cyclization relay of 3-indolymethanols and phosphites was disclosed, which afforded 1,2-oxaphospholoindole derivatives in moderate to good yields. Based on the experimental and computational studies, a mechanism involving radical addition and intramolecular cyclization cascade was proposed.
- Xu, Meng-Meng,Kou, Lu-Yao,Bao, Xiao-Guang,Xu, Xiao-Ping,Ji, Shun-Jun
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supporting information
p. 1915 - 1919
(2021/03/09)
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- Sulfonimide photo-acid generator with high acid yield
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The invention discloses a sulfonimide photo-acid generator with high acid yield. The sulfonimide photo-acid generator has a structure as shown in a general formula (A) in the description. The acid generator has high sensitivity to active energy rays with the wavelength of 300-450nm, particularly 365nm (I rays) and 405nm (H rays), and is good in solubility and strong in acidity.
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Paragraph 0176-0181
(2021/03/30)
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- KOH-mediated stereoselective alkylation of 3-bromooxindoles for the synthesis of 3,3′-disubstituted oxindoles with two contiguous all carbon quaternary centres
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The stereoselective synthesis of 3,3′-disubstituted oxindoles having all-carbon quaternary stereocenters has been achieved using KOH as a base with an excellent diastereomeric ratio (98?:?2). The practicability of the present methodology has been validated with the synthesis of a series of substrates in good to excellent yields. The aesthetic simplicity, accessibility, and eco-friendly base (KOH) have prompted the broader application of the present methodology in organic synthesis.
- Devi, Manju,Jadhav, Amol P.,Singh, Ravi P.
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supporting information
p. 8445 - 8448
(2021/05/25)
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- Rh(III)-Catalyzed [5 + 1] Annulation of Indole-enaminones with Diazo Compounds to Form Highly Functionalized Carbazoles
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A novel Rh(III)-catalyzed C-H activation/annulation cascade of indole-enaminones with diazo compounds was reported to construct diversely functionalized carbazole frameworks. The most notable characteristic is that this transformation could smoothly furnish a novel [5 + 1] cyclization product with good to excellent yields (up to 95%), accompanied by the thorough removal of acetyl and N,N-dimethyl groups of two substrates from the target products, rather than the normally expected [4 + 2] cyclization products.
- Jiang, Zhidong,Liu, Hong,Zhou, Jianhui,Zhou, Yu,Zhu, Haoran
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supporting information
p. 4406 - 4410
(2021/06/28)
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- Cascade Reaction to Selectively Synthesize Multifunctional Indole Derivatives by IrIII-Catalyzed C?H Activation
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An effective and condition-controlled way to synthesize with high selectivity a variety of functionalized indoles with potent biological properties has been developed. Notably, 2,4-dialkynyl indole products were obtained by direct double C?H bond alkynylation, whereas alkynyl at the C4 position could convert to carbonyl to generate 2-alkynyl-3,4-diacetyl indoles fast and effectively. Additionally, a one-pot relay catalytic reaction led to 2,5-di-alkynyl-3,4-diacetyl indoles when using a carbonyl group as the directing group and by controlling the type and quantity of additives. A possible mechanism was proposed based on many studies including deuterium-exchange experiments, the necessary conditions of product conversion, and the effect of water on the reaction.
- Chai, Xin-Yue,Xu, Hui-Bei,Dong, Lin
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supporting information
p. 13123 - 13127
(2021/08/13)
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- Z-Selective Fluoroalkenylation of (Hetero)Aromatic Systems by Iodonium Reagents in Palladium-Catalyzed Directed C?H Activation
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The direct and catalytic incorporation of fluorine containing molecular motifs into organic compounds resulting high-value added chemicals represents a rapidly evolving part of synthetic methodologies, thus this area is in the focus of pharmaceutical and agrochemical research. Herein we report a stereoselective procedure for direct fluorovinylation of aromatic and heteroaromatic scaffolds. This methodology development has been realized by palladium-catalyzed ortho C?H activation reaction of aniline derivatives featuring the regioselectivity via directing groups such as secondary of tertiary amides, ureas or ketones. The application of non-symmetrical aryl(fluoroalkenyl)-iodonium salts as fluoroalkenylating agents allowed mild reaction conditions in general for this transformation. The scope and limitations have been thoroughly investigated and the feasibility has been demonstrated by more than 50 examples.
- Bényei, Attila,Domján, Attila,Egyed, Orsolya,Gonda, Zsombor,Novák, Zoltán,Sályi, Gerg?,Tóth, Balázs L.
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supporting information
(2021/11/09)
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- Synthesis and antibacterial evaluation of (E)-1-(1H-indol-3-yl) ethanone O-benzyl oxime derivatives against MRSA and VRSA strains
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Infections caused due to multidrug resistant organisms have emerged as a constant menace to human health. Even though numerous antibiotics are currently available for treating infectious diseases, a great number of bacterial strains have acquired resistance to many of them. Among these, infections caused due to Staphylococcus aureus are predominant in adult and paediatric population. Indole is a prominent chemical scaffold found in many pharmacologically active natural products and synthetic drugs. A number of oxime ether containing compounds have attracted attention of researchers owing to their interesting biological properties. Current work details the synthesis of indole containing oxime ether derivatives and their evaluation for antimicrobial activity against a panel of bacterial and mycobacterial strains. Synthesized compounds demonstrated good to moderate activity against drug-resistant S. aureus including resistant to vancomycin. Among all, compound 5h was found to possess potent activity against susceptible as well as MRSA and VRSA strains of S. aureus with MIC of 1 μg/mL and 2–4 μg/mL respectively. In addition, compound 5h was found to be non-toxic to Vero cells and exhibited good selectivity index of >40. Further, 5h, E-9a and E-9b possessed good biofilm inhibition against S. aureus. With these assuring biological properties, synthesized compounds could be potential prospective antimicrobial agents.
- Akunuri, Ravikumar,Veerareddy, Vaishnavi,Kaul, Grace,Akhir, Abdul,Unnissa, Tanveer,Parupalli, Ramulu,Madhavi,Chopra, Sidharth,Nanduri, Srinivas
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- Site-Specific Oxidation of (sp3)C-C(sp3)/H Bonds by NaNO2/HCl
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A site-specific oxidation of (sp3)C-C(sp3) and (sp3)C-H bonds in aryl alkanes by the use of NaNO2/HCl was explored. The method is chemical-oxidant-free, transition-metal-free, uses water as the solvent, and proceeds under mild conditions, making it valuable and attractive to synthetic organic chemistry.
- Zhao, Jianyou,Shen, Tong,Sun, Zhihui,Wang, Nengyong,Yang, Le,Wu, Jintao,You, Huichao,Liu, Zhong-Quan
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p. 4057 - 4061
(2021/05/26)
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- A NaH-promoted N-detosylation reaction of diverse p-toluenesulfonamides
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A NaH-mediated detosylation reaction of various Ts-protected indoles, azaheterocycles, anilines and dibenzylamine was reported. The method features cheap reagent, convenient operations, mild reaction conditions and broad substrate scope. Moreover, this study revealed that the loading of NaH in tosylation reactions of nitrogen-containing compounds with NaH as a base in DMA or DMF should be controlled due to the possibility of adverse detosylation.
- Sun, Wanwan,Chen, Xiaobei,Hu, Ying,Geng, Huihui,Jiang, Yuanrui,Zhou, Yuxin,Zhu, Wenjing,Hu, Min,Hu, Haohua,Wang, Xingyi,Wang, Xinli,Zhang, Shilei,Hu, Yanwei
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supporting information
(2020/10/05)
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- NbCl5 and AgClO4 promoted regio-selective acylation of indoles
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In present study, an efficient and simple strategy towards chemo-selective and regio-selective acylation of indole using NbCl5 and AgClO4 catalyst are reported. This method utilizes the catalytic potentiality of NbCl5 and AgClO4 towards acylation of unprotected indoles in a synergistic manner. The combination of these catalytic system results into numerous advantages such as excellent yields of product, short reaction times and easier isolation of products.
- Kamble, Narendra R.,Pawar, Hari R.,Kamble, Vinod T.
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p. 317 - 321
(2020/01/08)
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- Weak Coordination Enabled Switchable C4-Alkenylation and Alkylation of Indoles with Allyl Alcohols
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A weak carbonyl coordination facilitated tunable reactivity between alkenylation and alkylation of indoles at the C4 C-H site is presented using readily accessible allylic alcohols in the presence of Rh catalysis by switching the additives or directing group. Exclusive site selectivity, functional group tolerance, and late-stage modifications are the important practical features.
- Banerjee, Sonbidya,De, Pinaki Bhusan,Mishra, Manmath,Pradhan, Sourav,Punniyamurthy, Tharmalingam
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supporting information
(2020/03/11)
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- Rhodium(III)-catalyzed C4-amidation of indole-oximes with dioxazolones: Via C-H activation
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A novel method for the Rh(III)-catalyzed oxime-directed C-H amidation of indoles with dioxazolones has been developed. This strategy provides an exclusive site selectivity and the directing group can be easily removed. This transformation features a wide substrate scope, good functional group tolerance and excellent yields, and may serve as a significant tool to construct structurally diverse indole derivatives for the screening of potential pharmaceuticals in the future. This journal is
- Deng, Ke-Zuan,Fu, Xiao-Pan,Ji, Ya-Fei,Tang, Shi-Biao,Wu, Gao-Rong,Xia, Cheng-Cai,Yang, Jin-Yue,Zhang, Li-Li
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supporting information
p. 7922 - 7931
(2020/11/02)
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- γ-Carboline synthesis enabled by Rh(iii)-catalysed regioselective C-H annulation
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A redox-neutral Rh(iii)-catalyzed C-H annulation of indolyl oximes was developed. Relying on the use of various alkynyl silanes as the terminal alkyne surrogates, the reaction exhibited a reverse regioselectivity, thus giving an exclusive and easy way for the synthesis of a wide range of substituent free γ-carbolines at C3 position with high efficiency. Deuterium-labelling experiments and kinetic analysis have preliminarily shed light on the working mode of this catalytic system. This journal is
- Jiang, Bo,Jia, Jingwen,Sun, Yufei,Wang, Yichun,Zeng, Jing,Bu, Xiubin,Shi, Liangliang,Sun, Xiaoying,Yang, Xiaobo
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supporting information
p. 13389 - 13392
(2020/11/10)
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- Ketone-Directed Cobalt(III)-Catalyzed Regioselective C2 Amidation of Indoles
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An efficient cobalt(III)-catalyzed method for the direct C-H amidation of unprotected indoles for 2-amino indole scaffold construction has been developed. With dioxazolone as the amidating reagent, a variety of 2-amino indole derivatives were achieved in moderate to excellent yields using an organic acid as the additive and a ketone as the directing group.
- Shi, Xinxia,Xu, Weiyan,Wang, Rongchao,Zeng, Xiaofei,Qiu, Huayu,Wang, Min
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p. 3911 - 3920
(2020/03/23)
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- Decarboxylative acylation of: N -free indoles enabled by a catalytic amount of copper catalyst and liquid-assisted grinding
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A facile decarboxylative acylation of N-free indoles with α-ketonates via liquid-assisted grinding was reported. The reaction requires only a catalytic amount of Cu(OAc)2·H2O in combination with O2 as the terminal oxidant to give various 3-acylindoles with high efficiency. Additionally, this new methodology was applicable to a gram-scale synthesis.
- Yu, Jingbo,Zhang, Chao,Yang, Xinjie,Su, Weike
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supporting information
p. 4446 - 4451
(2019/05/16)
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- Selective C-H acylation of indoles with α-oxocarboxylic acids at the C4 position by palladium catalysis
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The first Pd-catalyzed direct C-H acylation of indoles at the C4 position with α-oxocarboxylic acids using a ketone directing group is described. This reaction exhibits high regioselectivity with the tolerance of a wide scope of functional groups to afford diverse acylated indoles in moderate-to-good yields. The control experiments evidence the generation of acyl radicals via K2S2O8 promoted decarboxylation of α-oxocarboxylic acids and the involvement of a PdII/PdIV catalytic cycle. Importantly, the synthetically useful selectivity observed might be applied to prepare indole derivatives with anti-tumor activity as tubulin inhibitors.
- Zhang, Jitan,Wu, Manyi,Fan, Jian,Xu, Qiaoqiao,Xie, Meihua
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supporting information
p. 8102 - 8105
(2019/07/15)
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- Cobalt-Catalyzed Regioselective Direct C-4 Alkenylation of 3-Acetylindole with Michael Acceptors Using a Weakly Coordinating Functional Group
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Herein, we disclosed the first report on the selective C(4)-H functionalization of 3-acetylindole derivatives using first-row transition metal cobalt where an acetyl group is acting as a weakly coordinating directing group. Selective C(4)-H functionalization has been achieved using diverse Michael acceptors (acrylate and maleimide) simply by switching the additive from copper acetate to silver carbonate. Further the formation of a cobaltacycle intermediate was also detected through HRMS for mechanistic insight.
- Banjare, Shyam Kumar,Nanda, Tanmayee,Ravikumar
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supporting information
p. 8138 - 8143
(2019/10/14)
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- Insecticidal activity of indole derivatives against Plutella xylostella and selectivity to four non-target organisms
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The diamondback moth Plutella xylostella (Linnaeus, 1758) (Lepidoptera: Plutellidae) is a destructive pest of brassica crops of economic importance that have resistance to a range of insecticides. Indole derivates can exert diverse biological activities, and different effects may be obtained from small differences in their molecular structures. Indole is the parent substance of a large number of synthetic and natural compounds, such as plant and animal hormones. In the present study, we evaluate the insecticidal activity of 20 new synthesized indole derivatives against P. xylostella, and the selectivity of these derivatives against non-target hymenopteran beneficial arthropods: the pollinator Apis mellifera (Linnaeus, 1758) (Hymenoptera: Apidae), and the predators Polybia scutellaris (White, 1841), Polybia sericea (Olivier, 1791) and Polybia rejecta (Fabricius, 1798) (Hymenoptera: Vespidae). Bioassays were performed in the laboratory to determine the lethal and sublethal effects of the compounds on P. xylostella and to examine their selectivity to non-target organisms by topical application and foliar contact. The treatments consisted of two synthesized derivatives (most and least toxic), the positive control (deltamethrin) and the negative control (solvent). The synthesized compound 4e [1-(1H-indol-3-yl)hexan-1-one] showed high toxicity (via topical application and ingestion) and decreased the leaf consumption by P. xylostella, displaying a higher efficiency than the pyrethroid deltamethrin, widely used to control this pest. In addition, the synthesized indole derivatives were selective to the pollinator A. mellifera and the predators P. scutellaris, P. sericea and P. rejecta, none of which were affected by deltamethrin. Our results highlight the promising potential of the synthesized indole derivatives for the generation of new chemical compounds for P. xylostella management.
- Costa, ?ngela C. F.,Cavalcanti, Sócrates C. H.,Santana, Alisson S.,Lima, Ana P. S.,Brito, Thaysnara B.,Oliveira, Rafael R. B.,Macêdo, Nathália A.,Cristaldo, Paulo F.,Araújo, Ana Paula A.,Bacci, Leandro
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p. 973 - 982
(2019/08/26)
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- Weak Coordination-Guided Regioselective Direct Redox-Neutral C4 Allylation of Indoles with Morita-Baylis-Hillman Adducts
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A weak carbonyl coordination-guided regioselective C4 allylation of indoles is demonstrated using the versatile Morita-Baylis-Hillman adduct in the presence of Rh catalysts in a redox-neutral fashion. The substrate scope, functional group diversity, oxidant free character, mechanistic aspects, and synthetic utilities are important practical features.
- Pradhan, Sourav,De, Pinaki Bhusan,Punniyamurthy, Tharmalingam
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supporting information
p. 9898 - 9903
(2019/12/24)
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- Feasible selective synthesis of 3-Acetylindoles and 3-Acetoacetylindoles from β-ethylthio-β-indoly α, β-unsaturated ketones
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An efficient and selective synthesis of 3-acetyl free(N-H)/N-substituded indoles and 3-acetoacetyl free(N-H)/N-substituded indoles has been developed via the hydrolysis reaction of β-ethylthio-β-indoly α, β-unsaturated ketones in the presence of 3 equivalent of NaOH and 5 mol% of H2SO4, respectively. The procedure features easy operation, excellent yields, and high selectivity, compatibility and practicability.
- Wang, Wen-Ju,Yu, Hai-Feng
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p. 377 - 385
(2019/02/07)
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- Rhodium(III)-Catalyzed Regioselective Direct C4-Alkylation and C2-Annulation of Indoles: Straightforward Access to Indolopyridone
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A straightforward RhIII-catalyzed strategy was developed for the site-selective C4-alkylation and C2-annulation of indole by using electronically variable diazo esters. The transformation was accomplished with the assist of an oxime directing group at the C3 position of the indole core with wide scope and functional-group tolerance. The method directly provided an indolopyridone core. The selectivity was triggered by the reactivity of the diazo coupling partner.
- Biswas, Aniruddha,Samanta, Rajarshi
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p. 1426 - 1436
(2018/04/06)
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- Expanding the SAR of Nontoxic Antiplasmodial Indolyl-3-ethanone Ethers and Thioethers
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Despite major strides in reducing Plasmodium falciparum infections, this parasite still accounts for roughly half a million annual deaths. This problem is compounded by the decreased efficacy of artemisinin combination therapies. Therefore, the development and optimisation of novel antimalarial chemotypes is critical. In this study, we describe our strategic approach to optimise a class of previously reported antimalarials, resulting in the discovery of 1-(5-chloro-1H-indol-3-yl)-2-[(4-cyanophenyl)thio]ethanone (13) and 1-(5-chloro-1H-indol-3-yl)-2-[(4-nitrophenyl)thio]ethanone (14), whose activity was equipotent to that of chloroquine against the P. falciparum 3D7 strain. Furthermore, these compounds were found to be nontoxic to HeLa cells as well as being non-haemolytic to uninfected red blood cells. Intriguingly, several of our most promising compounds were found to be less active against the isogenic NF54 strain, highlighting possible issues with long-term dependability of malarial strains. Finally compound 14 displayed similar activity against both the NF54 and K1 strains, suggesting that it inhibits a pathway that is uncompromised by K1 resistance.
- Lunga, Mayibongwe J.,Chisango, Ruramai L.,Weyers, Carli,Isaacs, Michelle,Taylor, Dale,Edkins, Adrienne L.,Khanye, Setshaba D.,Hoppe, Heinrich C.,Veale, Clinton G. L.
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p. 1353 - 1362
(2018/07/13)
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- Meridianin D Analogues Display Antibiofilm Activity against MRSA and Increase Colistin Efficacy in Gram-Negative Bacteria
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In the last 30 years, development of new classes of antibiotics has slowed, increasing the necessity for new options to treat multidrug resistant bacterial infections. Development of antibiotic adjuvants that increase the effectiveness of currently available antibiotics is a promising alternative approach to classical antibiotic development. Reports of the ability of the natural product meridianin D to modulate bacterial behavior have been rare. Herein, we describe the ability of meridianin D to inhibit biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA) and to increase the potency of colistin against colistin-resistant and sensitive Gram-negative bacteria. Analogues were identified that are capable of inhibiting and dispersing MRSA biofilms and lowering the colistin MIC to below the CLSI breakpoint against Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli.
- Huggins, William M.,Barker, William T.,Baker, James T.,Hahn, Nicholas A.,Melander, Roberta J.,Melander, Christian
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p. 702 - 707
(2018/06/04)
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- An efficient synthesis and biological evaluation of novel analogues of natural product Cephalandole A: A new class of antimicrobial and antiplatelet agents
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Cephalandole A 2, a small indole alkaloid isolated from the Taiwanese orchid Cephalanceropsis gracilis (Orchidaceae), exhibits anticancer activity. Surprisingly, this natural product has not been evaluated for any other biological activity so far. To discover other novel potential of Cephalandole A 2, an efficient and economic synthetic protocol for novel Cephalandole A analogues 21a-o has been developed, in only 3 steps from using indole, and applied for their biological activity. Biological testing showed that Cephalandole A 2 and its novel analogues 21a-o exhibited potential antimicrobial and antiplatelet activity in preliminary assay. To the best of our knowledge, this is the first report of Cephalandole A 2 and its novel synthetic analogues 21a-o as a new class of antimicrobial and antiplatelet agents. In this study, 2 and other analogues i.e., 21b, 21d, 21i and 21o showed promising antimicrobial activity against the phytopathogenic bacteria and fungi. Cephalandole A 2, 21c, 21f and 21i, also showed potent antiplatelet activity.
- Sharma, Vashundhra,Jaiswal, Pradeep K.,Kumar, Krishan,Saran, Mukesh,Mathur, Manas,Swami, Ajit K.,Chaudhary, Sandeep
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- Palladium-catalyzed regioselective C-H fluoroalkylation of indoles at the C4-position
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An exclusive catalytic C4-selective fluoroalkylation of indoles with highly active (1H, 1H-perfluoroalkyl)mesityliodonium triflate has been described. The key to its high regioselectivity is the appropriate choice of an easily accessible, cheap and removable directing group at the C3 position in the presence of a Pd(OAc)2 catalyst. Besides indole fluoroalkylation, the application of this strategy in other heteroarenes such as benzo[b]thiophene is also described.
- Borah, Arun Jyoti,Shi, Zhuangzhi
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supporting information
p. 3945 - 3948
(2017/04/11)
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- Regiocontrolled direct C4 and C2-methyl thiolation of indoles under rhodium-catalyzed mild conditions
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A straightforward Rh(iii)-catalyzed general strategy was developed for the site-selective remote C4 (sp2) and C2 (sp3)-methyl thiolation of an indole core, keeping the oxime directing group at the C3 position. The transformation was accomplished under mild conditions with a wide scope and functional group tolerance. The directing group can easily be removed after operation. Methyl substitution at the C2 position of the indole core led to C2 (sp3)-methyl thiolation.
- Maity, Saurabh,Karmakar, Ujjwal,Samanta, Rajarshi
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supporting information
p. 12197 - 12200
(2017/11/16)
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- Br?nsted acidic ionic liquid-promoted direct C3-acylation of: N -unsubstituted indoles with acid anhydrides under microwave irradiation
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A green and efficient pathway for the synthesis of 3-acylindoles using a Br?nsted acidic ionic liquid as a catalyst has been developed for the first time. The C3-acylation of N-unsubstituted indoles with acid anhydrides affords the desired products in good to excellent yields with high regioselectivity under microwave irradiation. Moreover, the Br?nsted acidic ionic liquid can be recycled up to four times without significant loss of catalytic activity.
- Tran, Phuong Hoang,Duy Nguyen, Anh-Thanh,Nguyen, Hai Truong,Le, Thach Ngoc
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p. 54399 - 54406
(2017/12/12)
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- Chemical exploration of 4-(4-fluorobenzyl)piperidine fragment for the development of new tyrosinase inhibitors
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Tyrosinase is involved in the production of melanin through the hydroxylation of monophenols to o-diphenols. The role of this enzyme was extensively studied in order to identify new therapeutics preventing skin pigmentation and melanoma. In this work we initially identified the 3-(4-benzylpiperidin-1-yl)-1-(1H-indol-3-yl)propan-1-one (1a) as promising mushroom tyrosinase inhibitor (IC50= 252 μM). Then, several chemical modifications were performed and new analogues related to compound 1a were synthesized. Biochemical assays demonstrated that several obtained compounds proved to be effective inhibitors showing IC50values lower both than “lead compound” 1a and reference inhibitor kojic acid, as a well-known tyrosinase inhibitor. The inhibition kinetics analyzed by Lineweaver–Burk plots revealed that compounds 2 a-c and 10b act as non-competitive inhibitors while the most active inhibitor 2d (IC50= 7.56 μM) is a mixed-type inhibitor. Furthermore, experimental and computational structural studies were performed in order to clarify the binding mode of the derivative 2d.
- Ferro, Stefania,De Luca, Laura,Germanò, Maria Paola,Buemi, Maria Rosa,Ielo, Laura,Certo, Giovanna,Kanteev, Margarita,Fishman, Ayelet,Rapisarda, Antonio,Gitto, Rosaria
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p. 992 - 1001
(2016/11/11)
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- An efficient and green method for regio- and chemo-selective Friedel-Crafts acylations using a deep eutectic solvent ([CholineCl][ZnCl2]3)
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[CholineCl][ZnCl2]3, a deep eutectic solvent between choline chloride and ZnCl2, has been used as a dual function catalyst and green solvent for the Friedel-Crafts acylation of aromatic compounds instead of using the moisture-sensitive Lewis acids and volatile organic solvents. The reactions are performed with high yields under microwave irradiation with short reaction times for the synthesis of ketones. Interestingly, indole derivatives are regioselectively acylated in the 3-position under mild conditions with high yields without NH protection. Three new ketone products are synthesized. [CholineCl][ZnCl2]3 is easily synthesized from choline chloride and zinc chloride at a low cost, with easy purification and environmentally benign compounds. [CholineCl][ZnCl2]3 can be reused up to five times without loss of catalytic activity, making it ideal in industrial processes.
- Tran, Phuong Hoang,Nguyen, Hai Truong,Hansen, Poul Erik,Le, Thach Ngoc
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p. 37031 - 37038
(2016/05/24)
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- One-Step Dual Template Mediated Synthesis of Nanocrystalline Zeolites of Different Framework Structures
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A novel, dual template mediated, one-step direct synthesis route is reported here for the preparation of nanocrystalline zeolites of different framework structures (such as ZSM-5, mordenite, and sodalite). In this synthesis strategy, a suitably designed dicationic/tetra-cationic soft template was used along with a conventional zeolite structure director to obtain nanocrystalline zeolites with nanosheet morphology. Nanocrystalline zeolites exhibited large surface area, pore volume, and intercrystalline mesopores. The long hydrophobic chain containing a multiammonium template cooperatively participates in the zeolite crystallization process along with a conventional microporous zeolite structure director to form the ultrathin microporous zeolite framework, while the hydrophobic interaction between the long chains restricted the excessive growth of zeolites and induced the formation of intercrystalline mesopores. Nanocrystalline zeolites exhibited exceptionally high activity in the acid-catalyzed reactions involving large molecules when compared with conventional zeolites. This synthesis strategy can be extended for the preparation of zeolites of different framework structures or other porous materials in the future.
- Rani, Poonam,Srivastava, Rajendra,Satpati, Biswarup
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p. 3323 - 3333
(2016/06/14)
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- Synthesis and characterization of Trichloroisocyanouric acid functionalized mesoporous silica nanocomposite (SBA/TCCA) for the Acylation of Indole
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Trichloroisocyanouric acid (TCCA)-functionalized mesoporous silica nanocomposites (SBA/ TCCA) were synthesized and characterized for the acylation of indole. The uniform incorporation of TCCA inside the SBA-15 matrix was confirmed by standard characteriza
- Wilson, G Robin,Dubey, Amit
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p. 1285 - 1290
(2016/08/16)
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- Collective Synthesis of 3-Acylindoles, Indole-3-carboxylic Esters, Indole-3-sulfinic Acids, and 3-(Methylsulfonyl)indoles from Free (N-H) Indoles via Common N-Indolyl Triethylborate
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A general and direct C3 functionalization of free (N-H) indoles with readily available electrophiles such as acid chlorides, chloroformates, thionyl chloride, and methylsulfonyl chloride via a common N-indolyl triethylborate intermediate is reported. The reaction proceeds smoothly under mild conditions in up to 93% yield. Indoles with substituents at the C2, C4, C5, C6, and C7 positions are well tolerated. The easy accessibility of a variety of important 3-acylindoles, indole-3-carboxylic esters, indole-3-sulfinic acids, and 3-(methylsulfonyl)indoles demonstrates the high degree of compatibility and practicability of this method.
- Zhang, Zhi-Wei,Xue, Hong,Li, Hailing,Kang, Huaiping,Feng, Juan,Lin, Aijun,Liu, Shouxin
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supporting information
p. 3918 - 3921
(2016/08/16)
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- Decarboxylative/decarbonylative C3-acylation of indoles: Via photocatalysis: A simple and efficient route to 3-acylindoles
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A simple and efficient strategy for the preparation of 3-acylindoles via visible-light promoted C3-acylation of free (NH)- and N-substituted indoles with α-oxocarboxylic acids was developed. The reaction tolerates a wide range of functional groups, and the corresponding 3-acylindoles were obtained in high yields under mild conditions.
- Shi, Qing,Li, Pinhua,Zhu, Xianjin,Wang, Lei
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p. 4916 - 4923
(2016/11/04)
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- Synthesis of industrially important aromatic and heterocyclic ketones using hierarchical ZSM-5 and Beta zeolites
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Hierarchical ZSM-5 and Beta zeolites were investigated in the synthesis of wide range of industrially important aromatic/heterocyclic ketones by Friedel-Crafts acylation and benzoylation reactions. For comparative study, conventional ZSM-5 and Beta, and amorphous mesoporous Al-MCM-41 were investigated. Hierarchical zeolites were prepared by multi-ammonium structure directing agents whereas conventional zeolites were prepared by mono-ammonium structure directing agents. Among the catalysts investigated in this study, hierarchical Beta exhibited the highest reactant conversion in the acylation and benzoylation reactions. In this study, the systematic assessment of the catalytic activity of acid catalysts for wide range of aromatic and heterocyclic compounds is shown under one umbrella. To the best of our knowledge, these reactions over hierarchical zeolites (ZSM-5 and Beta) are reported here for the first time. Structure activity relationship is explained based on the physico-chemical properties, molecular size, reactivity of reactants, and reaction mechanism. Catalysts can be easily recovered and reused with negligible loss in the catalytic activity.
- Kore, Rajkumar,Srivastava, Rajendra,Satpati, Biswarup
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p. 129 - 141
(2015/09/28)
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- Meridianin derivatives as potent Dyrk1A inhibitors and neuroprotective agents
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Meridianins are a group of marine-derived indole alkaloids which are reported to possess kinase inhibitory activities. In the present Letter, we report synthesis of N1-substituted and C-ring modified meridianin derivatives and their evaluation as Dyrk1A inhibitors and neuroprotective agents. Among the library of 52 compounds screened, morpholinoyl linked derivative 26b and 2-nitro-4-trifluoromethyl phenyl sulfonyl derivative 29v displayed potent inhibition of Dyrk1A with IC50 values of 0.5 and 0.53 μM, respectively. The derivative 26b also inhibited Dyrk2 and Dyrk3 with IC50 values of 1.4 and 2.2 μM, respectively showing 2.2 and 4.4 fold selectivity for Dyrk1A with respect to Dyrk2 and Dyrk3. The compound 26b was not cytotoxic to human neuroblastoma SH-SY5Y cells (IC50 >100 μM) and it displayed significant neuroprotection against glutamate-induced neurotoxicity in these cells at 10 μM. Molecular modelling studies of compound 26b led to identification of key interactions in the binding site of Dyrk1A and the possible reasons for observed Dyrk1A selectivity over Dyrk2.
- Yadav, Rammohan R.,Sharma, Sadhana,Joshi, Prashant,Wani, Abubakar,Vishwakarma, Ram A.,Kumar, Ajay,Bharate, Sandip B.
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p. 2948 - 2952
(2015/06/22)
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- A simple, effective, green method for the regioselective 3-acylation of unprotected indoles
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A fast and green method is developed for regioselective acylation of indoles in the 3-position without the need for protection of the NH position. The method is based on Friedel-Crafts acylation using acid anhydrides. The method has been optimized, and Y(OTf)3 in catalytic amounts is found to be the best catalyst together with the commercially available ionic liquid [BMI]BF4 (1-butyl-3-methylimidazolium tetrafluoro-borate) as solvent. The reaction is completed in a very short time using monomode microwave irradiation. The catalyst can be reused up to four times without significant loss of activity. A range of substituted indoles are investigated as substrates, and thirteen new compounds have been synthesized.
- Tran, Phuong Hoang,Tran, Hai Ngoc,Hansen, Poul Erik,Do, Mai Hoang Ngoc,Le, Thach Ngoc
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p. 19605 - 19619
(2015/11/27)
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- Reactions of nitrilium salts with indole and pyrrole and their derivatives in the synthesis of imines, ketones and secondary amines
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Abstract Reactions of N-methyl- and N-ethyl-nitrilium salts with indole and pyrrole and their derivatives yield imines or imine salts in good yields. The related imines are obtained from the salts after careful basification and hydrolysis of the imine salts or the imines by heating with aqueous base give the related ketones in good yields. Alternatively, the imine salts can be reduced using sodium borohydride in methanol to give the related secondary amines.
- Giles, Robert G.,Heaney, Harry,Plater, M. John
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p. 7367 - 7385
(2015/08/24)
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- Targeting GluN2B-containing N-methyl- D -aspartate receptors: Design, synthesis, and binding affinity evaluation of novel 3-substituted indoles
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In an effort to improve our knowledge about structure-affinity relationships (SARs) for a class of 3-substituted-indole derivatives as GluN2B-containing N-methyl-D-aspartate-type receptor (NMDAR) ligands, we herein describe the design, synthesis, and preliminary screening of a new series of molecules. The in vitro determination of binding affinities suggested that 5-hydroxy- and 6-hydroxyindole derivatives 12 and 13 were active ligands. Generally, the novel compounds proved to be less potent than their homologs previously reported as promising neuroprotective agents. In fact, our lead compound 3-(4-benzylpiperidin-1-yl)-1-(5-hydroxy-1H-indol-3-yl)ethan-1-one (2) was about 10-fold more active than the new propan-1-one derivative (12). To rationalize the low potency of the new analog 12, docking studies were also performed and the in silico results were consistent with the in vitro data.
- Buemi, Maria Rosa,De Luca, Laura,Ferro, Stefania,Gitto, Rosaria
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p. 533 - 539
(2014/08/18)
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- Acid-catalyzed acylation reaction via C-C bond cleavage: A facile and mechanistically defined approach to synthesize 3-acylindoles
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A facile acid-catalyzed acylation of indoles with 1,3-dione as an eco-friendly acylating agent was developed. This protocol combines C-C bond cleavage and heterocyclic C-H bond functionalization to form new C-C bonds. Based on the detailed mechanistic studies, a credible mechanistic pathway was proposed. This journal is
- Xing, Qi,Li, Pan,Lv, Hui,Lang, Rui,Xia, Chungu,Li, Fuwei
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supporting information
p. 12181 - 12184
(2014/12/11)
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- Synthesis of 3-acylindoles via decarboxylative cross-coupling reaction of free (NH) indoles with α-oxocarboxylic acids
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A convenient and general method for acylation of free (NH) indoles via palladium-catalyzed decarboxylative cross-coupling reaction was developed. This process provided a useful method for the preparation of diverse 3-acylindoles in high yields utilizing a reaction with readily accessible reactants under mild conditions.
- Gu, Li-Jun,Liu, Ji-Yan,Zhang, Li-Zhu,Xiong, Yong,Wang, Rui
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- Meridianin G and its analogs as antimalarial agents
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The marine-derived indole alkaloids meridianin C and G and their N1-substituted and C-ring modified analogs were synthesized and screened for antiprotozoal and antimicrobial activities. Meridianin C and G showed antimalarial activity against both chloroquine-resistant (D6) as well as sensitive (W2) clones of Plasmodium falciparum with IC50 values in the range of 4.4 to 14.4 μM. Meridianin G showed better activity against the W2 clone, showing a higher selectivity index >24.1. Among the analogs, N1-morpholinoyl meridianin C analog displayed antimalarial activity against both clones, showing selectivity indices up to 25.1. Meridianin C along with a few other analogs showed weak to moderate antileishmanial activity against Leishmania donovani promastigotes, the best analog being a C-ring modified 5-iodo meridianin showing an IC50 of 9.17 μM. A few compounds also showed mild antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus, and antifungal activity against Cryptococcus neoformans.
- Bharate, Sandip B.,Yadav, Rammohan R.,Khan, Shabana I.,Tekwani, Babu L.,Jacob, Melissa R.,Khan, Ikhlas A.,Vishwakarma, Ram A.
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supporting information
p. 1042 - 1048
(2013/07/27)
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- Iron powder promoted regio-selective friedel-crafts acylation of indole under solvent-free conditions
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A facile, efficient and environment-friendly protocol for the regioselective synthesis of 3-acyl indoles has been developed by one-pot catalytic Friedel-Crafts acylation of indole in presence of the iron powder as catalyst under solvent-free conditions at room temperature.
- Zhang, Lirong,Yi, Fengping,Zou, Jianzhong,Qu, Shaoyan
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p. 6117 - 6120
(2013/07/26)
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- Synthesis of 3-acylindoles by palladium-catalyzed acylation of free (N-H) indoles with nitriles
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An efficient palladium-catalyzed synthesis of 3-acylindoles using free (N-H) indoles and nitriles has been developed. The acylation reaction proceeded well under the Pd(OAc)2/2,2′-bipyridine system and with d-(+)-camphorsulfonic acid as the additive. A possible mechanism involving carbopalladation of nitriles and subsequent hydrolysis of ketimines is proposed.
- Jiang, Tao-Shan,Wang, Guan-Wu
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supporting information
p. 788 - 791
(2013/03/29)
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- Microwave-assisted Friedel-Crafts acylation of indole with acetic anhydride over tungstophosphoric acid modified Hβ zeolite
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Friedel-Crafts acylation of indole with acetic anhydride has been carried out over zeolites under microwave and conventional heating, respectively. A tungstophosphoric acid modified Hβ (PW-Hβ) zeolite showed better catalytic performance than parent Hβ zeolite due to its higher amount of strongly acidic sites and lower amount of Lewis acid sites, confirmed from NH3 temperature-programmed desorption (NH3-TPD) and Fourier Transform Infrared Spectrometer after adsorption of pyridine (Py-IR). Particularly, microwave radiation was found to make this transformation not only more efficient but also selective to 3-acetylindole compared with conventional heating. Furthermore, PW-Hβ has shown good stability in this reaction.
- Bai, Guoyi,Li, Tianyu,Yang, Yonghui,Zhang, Huanhuan,Lan, Xingwang,Li, Fei,Han, Jie,Ma, Zheng,Chen, Qingzhi,Chen, Guofeng
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p. 114 - 117
(2013/01/15)
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- A systematic study of two complementary protocols allowing the general, mild and efficient deprotection of N-pivaloylindoles
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Two mild and general protocols for the high-yielding deprotection of indoles and related fused heterocyclic systems are described, involving either hydride transfer from LDA or hydrolysis by the DBU-water system. Both methods were shown to tolerate a wide variety of substituents and functional groups, but the hydrolytic one proved to be particularly general, being compatible with 2-alkyl substituents, aldehydes, ketones, carboxylic acids, halogens, ethers, amides and esters. Yields were normally excellent in both cases, but were usually slightly higher for the reductive method. Taken together, these two protocols provide a general solution to the problem of pivaloyindole deprotection.
- Ruiz, Míriam,Sánchez, J. Domingo,López-Alvarado, Pilar,Menéndez, J. Carlos
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experimental part
p. 705 - 710
(2012/01/06)
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- Regioselective Friedel-Crafts acylation of indoles catalysed by zinc oxide in an ionic liquid
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A facile method for the regioselective Friedel-Crafts acylation of indoles with acyl chlorides catalysed by zinc oxide in an ionic liquid medium has been developed. The corresponding 3-acylindoles were obtained in good to high yields under mild reaction conditions. Zinc oxide, which is easily available and requires no special handling procedures, is an efficient catalyst for acylation of indoles.
- Zhang, Li-Rong,Yi, Feng-Ping,Zou, Jian-Zhong,Zhang, Xuan,Wang, Zhen
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p. 600 - 602,3
(2020/09/16)
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- Antifungal agents. Part 3: Synthesis and antifungal activities of 3-acylindole analogs against phytopathogenic fungi in vitro
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To find more potent antifungal compounds, twenty 3-acylindole analogs were synthesized and bio-evaluated for their antifungal activities against seven phytopathogenic fungi. Structure-activity relationships investigations revealed that 4- or 6-methyl and 3-acetyl or propionyl groups were the important structural properties of 3-acylindoles for the activities. Especially 4-methyl-3-propionylindole, 12, displayed the more potent activities than hymexazol, a commercially available agricultural fungicide, and might be considered as a new promising lead candidate for further design and synthesis of agricultural fungicides.
- Xu, Hui,Bin Yang, Wen,Wang, Qin
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experimental part
p. 864 - 868
(2012/06/29)
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